Posted by SLS on July 18, 2008, at 11:56:11
In reply to Re: How long for an adequate tianeptine trial? » SLS, posted by Quintal on July 18, 2008, at 9:28:15
Hi Quintal.
Thanks for such a thoughtful response.
Tianeptine is one of the few major antidepressants that I have not tried. I know nothing of its personality.
> Thank you for your advice. My depression fluctates anyway, that's why I adjust the dose. If you ever try tianeptine you might find, like me, that it works in a different way to other antidepressants, and I don't just mean the mechanism. Tianeptine can be taken as required. I don't think SSRIs or any other conventional class of antidepressants can be used in this way. For me tianeptine belongs in the same 'class' as benzos, opiates and amphetamines in that I can usually guage how much I need to acheive the desired effect. I've never alterd the dose of any other antidepressant like this, bar Parnate, and there's reason for that.
Very interesting. That's a great analogy between drug classes.
> As far as homeostatis is concerned, I think that might actually be a contributing factor in antidepressant 'poop-out', and thereby treatment resistance.
I've heard this before, and I am still undecided. Your point is well taken, and it is an important issue. It's funny, but one of our posters, Noa, first presented this idea several years ago. I was struck by it, and it does make sense. Of course, making sense does not guarantee that the conclusion arrived at is accurate.
> The body eventually adapts to a steady, controlled dose of a foreign substance (possibly a toxin) over time. The fact that the brain can eventually reach equillibrium undermines the efficacy of sleeping tablets, painkillers, benzos and I believe antidepressants too.
There is no doubt that antidepressants extend the time before relapse. SSRIs seem to be the antidepressants most likely to poop-out. Yet, Nardil will poop out for some people, too. Perhaps there is a counterproductive drift in gene expression that is responsible for this. That is really what it comes down to.
Taking into consideration the putative mechanism of action of tianeptine being the reverse of SSRIs, I often wonder if "pushing" the system in either direction results in the same thing, namely, to force adjustments to be made in dynamics such that the resultant state represents a reset of gene expression. The resultant compensatory events produce a new phenotype that more approximates the ratios normally designed by the genotype. It is like the neurons saying, "Ok, we've been pushed out of our homeostatic zone [by an antidepressant]. Now, lets compensate to bring the system back into equilibrium. I guess we should use the original blueprints (genes) to arrive at the position we were originally designed to be at." Absolute numbers are different, but ratios are the same.
What do I know? This might be a very silly idea.
> I sometimes think it's actually the switch between antidepressants, and the resulting disruption, that restores an antidepressant response (at least initially) in some people who have experienced antidepressant poop-out. Keeps the brain on its toes.
This is sound reasoning, but doesn't explain the decades for which many people have been stabilized on an antidepressant, only to relapse upon an attempt to discontinue treatment. NIMH saw this with clorgyline, an MAOI antidepressant when the drug became no longer available, and patients relapsed within weeks to a few months after discontinuation. However, the fact that Nardil poop-out can be remediated by stopping the drug for three months and then restarting it is in agreement with your notion of keeping the brain on its toes. It is also in agreement with mine. The idea is to provoke the brain into compensating for a change in equilibrium, perhaps by using new set points of gene expression that are higher or lower, but that are at nominal ratios. This idea is really pretty complex in the details, but simple in concept.
What other ideas do you have regarding the neuroscience of affective disorders? Inquiring minds want to know.
:-)
- Scott
poster:SLS
thread:840180
URL: http://www.dr-bob.org/babble/20080718/msgs/840458.html