Posted by Sean on September 28, 1999, at 12:18:16
In reply to All that's old is new again..., posted by Adam on September 28, 1999, at 0:30:01
> Ah, progress.
>
> The last decade has seen an incredible increase in the number and kind of antidepressant medications. Today we have SSRIs, NARIs, SNRIs, RIMAs, alpha-adrenergic receptor agonists, serotonin receptor antagonists, anticonvulsants, and heavens knows what else. And of course there are the old tricyclics and the MAOI inhibitors, classes of drugs that, serendipitously, were found to relieve depression. The newer drugs, sought out specifically for their potential antidepressant effects, have promised to meet or exceed the efficacy of the old with fewer/no side effects, and one cannot help but be struck by the hype surrounding Prozac and its siblings at the beginning of the decade to see how perilously attractive such promises have been.
> But it seems to me that the hype has largely belied the real value of the newer drugs when compared to the old, and with many American doctors now embracing polypharmacy, when such a short while ago laser-guided monotherapies were all the rage, I can’t help but think we are largely trying to mimic with lots of new drugs what was done very effectively with the old ones. And not always with much success, or at least, when the possible drug interactions and side effects start piling up, with fewer clear advantages than one would hope.
> Prozac once seemed like a miracle. Now, as reboxetine nears approval, I’ve read many articles where doctors have disparaged the SSRIs for their lack of robustness in treating severe depression, and how a safe NARI is thus so eagerly awaited here. SSRIs often deaden peoples emotions, they say, while reboxetine improves drive, social functioning and so on. Hopefully the future rush to prescribe NARIs will prove to be more than a giant fad.
> There is little that is alluring about, say, an MAOI. A host of possible side effects, and, of course, the dietary restrictions and the potential for lethal drug interactions. Yet they are still prescribed, and, it would seem through my conversations with some pdocs old enough to remember the days when the MAOIs and tricyclics were all there really was, pack more of an antidepressant punch than anything available today. I am currently enrolled in an MAOI study, and have had a chance to talk to the principle investigator, who, not being one to mince words, has described a full response to an MAOI as feeling “fantastic” in a way that no other antidepressant can match. I’ve read with interest the stories of the first patients in a VA hospital being treated for tuberculosis with iproniazid who were literally described by one doctor as “dancing in the aisles”. It’s hard to argue with such observations, especially when they are so unexpected. I find the results of Eli Lily-funded studies less compelling. I am disconcerted by meta analyses of recent antidepressant clinical trials that estimate the placebo effect to account for around 80% of the therapeutic effect.
> Like I said, I’m currently in a study where an MAOI (in this case selegiline, perhaps a more dubious MAOI in terms of efficacy in treating depression) is being delivered via a transdermal “patch” system to get around dietary restrictions. I’m hoping that this idea shows promise and can be applied to other MAOIs, if not ones currently available, then ones to be developed in the future. It seems in the hopes of avoiding the adverse effects of this old class of drugs, many have abandoned it altogether, and nearly all the research out there is on the newer classes. Maybe if the transdermal system works it will help revive some interest in the MAOIs, even if a transdermal system cannot always be used. If selegiline doesn’t work for me, chances are I will try Parnate, and sadly bid good-bye to pepperoni pizzas and a good pint of Guinness. Such has been the vain pursuit of real help from the newer meds that I didn’t make this transition long ago, and I may have suffered needlessly in the interim because none of my prior doctors even considered an MAOI, or saw the possible advantages.
>
> Well, those are my thoughts. What are yours?In general, I agree with everything said here. But
I think we might all accept that having more drugs
in the pharmacopia is better than fewer, and, the
side effects of TCA's and MAOI's were for some
people, very problematic compared to SSRI's.One theory I have about AD's (which is probably
totally wrong, but based on personal observations
of my own affect and perceptual acuity while on
various meds) is that the AD prescribed is not
directly causing the effect. To me it *feels*
like a secondary reaction to the drug is what
eventually causes the relief. Also, I have noticed
that I actually feel best right as the AD is
having an effect - AND - right after I stop it.Maybe drug poop-out is simply a re-establishment
of the primary dysfunction after the brain has
a chance to adjust to the new chemical environment.
Then, when you go off the AD, this state is
disrupted and you have a brief AD effect.Why am I rambling on about this? All these drugs,
old and new, generally operate on the three
amine systems: serotonin, dopamine, and
norepinephrine. The subjective "quality" of the
response to perturbing one or more of these
systems is what differentiates the "feel" of the AD.
BUT, none of these drugs really get to the root
of the problem (in my opinion). They simply jar
the brain for a while and then you wind up back
where you started.What these drug company people need to do (again
in my likely ridiculous opinion!) is to look more
at the process of *reaction* to the various drugs
and why such different substances can cause a
similar change in mood. I think the current AD's
are probably operating like a scaled-down form
of ECT.The delay in AD response seems to be linked to
the necessity of the brain to literally change
certain genes in the cells that create transmitters
and receptors. A drug that had a direct effect on
these transcription processes would likely have
a quick onset and lasting result.In conclusion (hee hee hee!) I'm kind of sick of all
the available drugs because they still do not
deal with depression directly. This makes all the
maketing hype particulary offensive. I mean,
come on Pfizer, Lilly, and Merck: wake up and smell
the genome...Sean.
poster:Sean
thread:12171
URL: http://www.dr-bob.org/babble/19990914/msgs/12195.html