Posted by Ritch on August 10, 2002, at 11:08:40
In reply to Re: Interesting article » Ritch, posted by SLS on August 10, 2002, at 9:37:13
> Hi Mitch.
>
> How have you been doing?
I have been doing better this summer than I have in *many* summers. I think the L-tyrosine and low-dose Depakote+Effexor+Wellbutrin is making a big difference this time. I am sleeping Ok, and I feel almost normal for a time of year I typically am very depressed. Of course, I am forcing myself to exercise a lot more-so that is contributing too.>
> > It would be nice if more pharm. companies would be interested in attempting to market meds that are already available in other countries that could be helpful here. I am thinking of moclobemide for one (why doesn't Roche try to get FDA approval here?).
>
> First of all, it is my impression that moclobemide is really not a terribly effective drug - either for depression or social-phobia. Of course, some people respond well to it, but the non-selective irreversible MAOIs generally demonstrate superior efficacy. It is certainly worth a try, though. You never know, right?
>
> - Don't give up on moclobemide until you reach 1200mg.
> - Do not eat any more than 50mg of tyramine at any one meal.
>
> I would be very interested to know what drugs you would combine with moclobemide. Zyprexa would be interesting.
>
> I tried moclobemide in December, 1996. I reacted very, very badly to it. It exacerbated my depression to a degree worse than I have ever experienced. I was curled up in a fetal position on the couch for days, wimpering in pain. No thoughts. Just mental pain.
>
> Roche conducted trials of moclobemide in the US for the indication of social-phobia. I guess they figured they had a better chance of getting the FDA to approve a drug for an indication for which few drugs had yet been approved. The results were poor. I spoke to the head of the US moclobemide project just before it was discontinued. He told me that it was dead and that the trials had been terminated. I doubt they will revisit it.I was considering moclobemide precisely because it *is* weak. I hyper-respond to antidepressants, due to bipolar and to general med sensitivities. It wouldn't surprise me at all if I responded well to 75mg twice daily! You see I am only taking 12.5mg of Effexor and 18.75mg of Wellbutrin right now. Any more of either one of those disrupts my sleep too much, or makes me too tired or too wired during the day. The trouble I have with antidepressants isn't really response, it is tolerance and hypomania. Also, stimulants and short half-life AD's like Effexor seem to work better than longer-half life AD's. The longer half-life ones seem to cause a lot of early morning awakenings and resultant daytime drowsiness. When that happens a lot, my cycling tends to worsen.
>
> > Also, the active metabolite of nortriptyline (I think E-10 OH-nortriptyline),
>
> Isn't the parent compound active? What are the differences between them? What other drugs downregulate 5-HT receptors? In what ways does this help with depression? Is it simply an observed association or is there a hypothesis as to how it contributes to producing a remission?OH, I was just thinking out loud about a medline abstract I read regarding E-10 OH-NT a long time ago. They recommended looking into developing it as a possible antidepressant. The 5-HT downregulation is common with many antidepressants-I think they were primarily looking at the anxiolytic effects. Nortripytline (the parent compound) *is* active. NT just happens to be the only tricyclic that I have had any success with. Amitriptyline is it's parent. Another study was done where they gave AMI to a group of people and measured the relative balance of AMI and NT in their blood. The people that had the highest remission rates had the highest NT blood levels. How active E-10 OH-NT compared to *it's* parent we probably will never know.
>
> Thanks.
>
> > Why can't that be developed? Marketing active metabolits of older drugs is becoming more common (fexofenadine and cetirizine, ie.).
>
> For every 1 drug brought to market, 100 are synthesized, researched, and discarded for various reasons, including projected profitability. It costs 800 million dollars and 12 years to get a drug approved by the FDA. I imagine there are a few miracle drugs that have ended up in landfills.
>
>
> - Scott
>
>
poster:Ritch
thread:109458
URL: http://www.dr-bob.org/babble/20020807/msgs/115931.html