Posted by West on August 10, 2008, at 7:52:28
In reply to Re: SSRI vs SNRI - Efficacy Comparison Article (lo, posted by dcruik518 on August 8, 2008, at 12:55:28
> Scott,
>
> Thanks for this excellent and apropos article. I think the truth is that none of the so-called SNRI's are really any more effective than the SSRI's, but based on what I've read the main reason is that they do not sufficiently boost Norepinephrine.
>
> I'm not sure this author is making that argument, though, and maybe that's why he doens't bring up potential solutions--namely adding a very strong NE tricyclic like Nortryptyline or Desimpramine to an SSRI. There are also studies that show that clomipramine which is a truly "balanced" SNRI is superior for severe depression than Effexor; (Clomipramine gets an underserved bad rap in my opinion; i worked quit well for me when I took it, once I got past the initial grogginess.) I'm currently taking Pristiq which may be a more potent NE reuptake inhibitor at lower doses than Effexor, but I'm a bit skeptical since Wyeth obviously developed the drug solely for profit reasons after the effexor patent has expired. Still, so far it seems to be helping a bit, and I like your idea of adding Nortryptyline to it.
>
> A thought: Isn't it probable that the drugs and drug combos that work best would hit all three neurotransmitters? For instance:
>
> MAOIs, (I wonder if Parnate might be a better/healthier choice, since its causes much less weight gain than Nardil)
>
> Zoloft + Nortryptyline (+ Wellbutrin)
> (Note that Zoloft is the only SSRI that has significant dopamine reuptake inhibition activity on its own)
>
> Anyway, thanks again for the enlightening article.
>
> Dwight
Actually sertraline's effect on dopamine is negligible in vivo, though tables like this one would lead you to think otherwise:http://findarticles.com/p/articles/mi_m0689/is_12_52/ai_111614764/pg_5
From it would postulate that bupropion is primarily a DRi with the affinities at 25:6.719:1 for DA:Na:5HT respectively. However, its effect on dopamine in vivo is peripheral to its effect on norepinephrine, and is primarily a noradrenergic drug.
Bupropion and its primary metabolite hydroxybupropion decrease the reuptake of norepinephrine and dopamine in rat and mouse synaptosomes. Acute administration also reduces firing of dopamine and norepinephrine neurons in the brain of the rat stems* which is consistent with an increase in synaptic levels of DA and NA. In turn this inhibits neuronal firing by autoreceptor-mediated negative feedback mechanism. 2 studies mention rises in extracellular DA and NA using microdialysis.
MAOIs are notoriusly side effect heavy, they remain efficacious antidepressants but are best avoided where prudent use of newer generation/tricyclic combinations are tolerated.
poster:West
thread:844518
URL: http://www.dr-bob.org/babble/20080805/msgs/845278.html